The leading causes of low vision and blindness, which include cataract, glaucoma, age-related macular degeneration, corneal dystrophy, and diabetic retinopathy, affect over 40 million Americans and have an estimated annual cost of $25 billion for clinical diagnosis and treatment. The prevalence of visual impairment in adults 40 years and older in the United States is above 3.5% and expected to increase markedly due to population aging. Although several recent studies have demonstrated the utility of intraoperative OCT (iOCT) for verifying completion of surgical goals, real-time iOCT feedback is not currently used to guide ophthalmic surgery because of several fundamental limitations of current-generation iOCT technology: (1) Serial cross-sectional OCT does not provide sufficient spatial position and orientation feedback to guide surgery. (2) Video-rate volumetric OCT trades-off sampling density with field-of-view and consistent alignment of small static OCT fields to regions-of-interest is prohibitively difficult during surgical maneuvers. (3) Co-registration of volumetric OCT data with the surgical field is challenging because fiducials are often confounded by the non-uniform illumination and contrast of surgical microscopy. (4) Real-time volumetric OCT visualization is complex and time-consuming, requiring cross-sectional fly-throughs or computationally expensive renderings that occlude subsurface features. We recently developed multimodal intraoperative spectrally encoded coherence tomography and reflectometry (iSECTR) technologies that allows for simultaneous and intrinsically co-registered en face reflectance and cross- sectional OCT imaging. We hypothesize that (1) imaging data from 4D iSECTR of surgical dynamics will benefit surgical decision-making and lead to improved functional outcomes; and (2) integration of imaging, registration, segmentation, and feedback using heads-up display (HUD) visualization will enhance existing and enable novel surgical maneuvers. We have assembled a multidisciplinary team of engineers and clinicians to perform foundational ex vivo and in vivo imaging studies to (1) quantitatively assess the safety and utility of 4D iSECTR- based surgical feedback; and (2) develop novel technologies, feedback mechanisms, and maneuvers that integrate volumetric iSECTR data for image-guided ophthalmic surgery. Comprehensive 4D imaging of tissue- instrument interaction dynamics (AIM 1) provides unprecedent data on structural changes resulting from surgical manipulation that may be predictive of post-operative functional outcomes and enable image-based interrogation of biomechanics and personalized surgical planning. Real-time surgical visualization and guidance (AIM 2) may improve success rates of conventional surgical interventions as well as next-generation gene and stem cell therapies. Image-guided surgery also may be compatible with robotic-assistance and telemanipulation in wide- ranging surgical specialties outside of ophthalmology. Quantitative analysis of intraoperative imaging performance, utility, and clinical value (AIM 3) will motivate future technology development and clinical adoption.